Cargando…

Extracellular matrix regulates force transduction at VE-cadherin junctions

Increased tension on VE-cadherin (VE-cad) complexes activates adaptive cell stiffening and local cytoskeletal reinforcement–-two key signatures of intercellular mechanotransduction. Here we demonstrate that tugging on VE-cad receptors initiates a cascade that results in downstream integrin activatio...

Descripción completa

Detalles Bibliográficos
Autores principales: Kong, Xinyu, Kapustka, Adrian, Sullivan, Brendan, Schwarz, Gregory J., Leckband, Deborah E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582804/
https://www.ncbi.nlm.nih.gov/pubmed/35653290
http://dx.doi.org/10.1091/mbc.E22-03-0075
_version_ 1784812924976496640
author Kong, Xinyu
Kapustka, Adrian
Sullivan, Brendan
Schwarz, Gregory J.
Leckband, Deborah E.
author_facet Kong, Xinyu
Kapustka, Adrian
Sullivan, Brendan
Schwarz, Gregory J.
Leckband, Deborah E.
author_sort Kong, Xinyu
collection PubMed
description Increased tension on VE-cadherin (VE-cad) complexes activates adaptive cell stiffening and local cytoskeletal reinforcement–-two key signatures of intercellular mechanotransduction. Here we demonstrate that tugging on VE-cad receptors initiates a cascade that results in downstream integrin activation. The formation of new integrin adhesions potentiates vinculin and actin recruitment to mechanically reinforce stressed cadherin adhesions. This cascade differs from documented antagonistic effects of integrins on intercellular junctions. We identify focal adhesion kinase, Abl kinase, and RhoA GTPase as key components of the positive feedback loop. Results further show that a consequence of integrin involvement is the sensitization of intercellular force transduction to the extracellular matrix (ECM) not by regulating junctional tension but by altering signal cascades that reinforce cell–cell adhesions. On type 1 collagen or fibronectin substrates, integrin subtypes α2β1 and α5β1, respectively, differentially control actin remodeling at VE-cad adhesions. Specifically, ECM-dependent differences in VE-cad force transduction mirror differences in the rigidity sensing mechanisms of α2β1 and α5β1 integrins. The findings verify the role of integrins in VE-cad force transduction and uncover a previously unappreciated mechanism by which the ECM impacts the mechanical reinforcement of interendothelial junctions.
format Online
Article
Text
id pubmed-9582804
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-95828042022-11-22 Extracellular matrix regulates force transduction at VE-cadherin junctions Kong, Xinyu Kapustka, Adrian Sullivan, Brendan Schwarz, Gregory J. Leckband, Deborah E. Mol Biol Cell Articles Increased tension on VE-cadherin (VE-cad) complexes activates adaptive cell stiffening and local cytoskeletal reinforcement–-two key signatures of intercellular mechanotransduction. Here we demonstrate that tugging on VE-cad receptors initiates a cascade that results in downstream integrin activation. The formation of new integrin adhesions potentiates vinculin and actin recruitment to mechanically reinforce stressed cadherin adhesions. This cascade differs from documented antagonistic effects of integrins on intercellular junctions. We identify focal adhesion kinase, Abl kinase, and RhoA GTPase as key components of the positive feedback loop. Results further show that a consequence of integrin involvement is the sensitization of intercellular force transduction to the extracellular matrix (ECM) not by regulating junctional tension but by altering signal cascades that reinforce cell–cell adhesions. On type 1 collagen or fibronectin substrates, integrin subtypes α2β1 and α5β1, respectively, differentially control actin remodeling at VE-cad adhesions. Specifically, ECM-dependent differences in VE-cad force transduction mirror differences in the rigidity sensing mechanisms of α2β1 and α5β1 integrins. The findings verify the role of integrins in VE-cad force transduction and uncover a previously unappreciated mechanism by which the ECM impacts the mechanical reinforcement of interendothelial junctions. The American Society for Cell Biology 2022-09-07 /pmc/articles/PMC9582804/ /pubmed/35653290 http://dx.doi.org/10.1091/mbc.E22-03-0075 Text en © 2022 Kong et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License.
spellingShingle Articles
Kong, Xinyu
Kapustka, Adrian
Sullivan, Brendan
Schwarz, Gregory J.
Leckband, Deborah E.
Extracellular matrix regulates force transduction at VE-cadherin junctions
title Extracellular matrix regulates force transduction at VE-cadherin junctions
title_full Extracellular matrix regulates force transduction at VE-cadherin junctions
title_fullStr Extracellular matrix regulates force transduction at VE-cadherin junctions
title_full_unstemmed Extracellular matrix regulates force transduction at VE-cadherin junctions
title_short Extracellular matrix regulates force transduction at VE-cadherin junctions
title_sort extracellular matrix regulates force transduction at ve-cadherin junctions
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582804/
https://www.ncbi.nlm.nih.gov/pubmed/35653290
http://dx.doi.org/10.1091/mbc.E22-03-0075
work_keys_str_mv AT kongxinyu extracellularmatrixregulatesforcetransductionatvecadherinjunctions
AT kapustkaadrian extracellularmatrixregulatesforcetransductionatvecadherinjunctions
AT sullivanbrendan extracellularmatrixregulatesforcetransductionatvecadherinjunctions
AT schwarzgregoryj extracellularmatrixregulatesforcetransductionatvecadherinjunctions
AT leckbanddeborahe extracellularmatrixregulatesforcetransductionatvecadherinjunctions